This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The National Institutes of Health has established the COPD Clinical Research Network to seek new COPD therapies. COPD (chronic obstructive pulmonary disease, also called chronic bronchitis and emphysema) is a chronic lung disease usually caused by cigarette smoking and is the 4th leading cause of death in the United States. Ten University-based centers around the United States constitute the Network. Exacerbations of chronic obstructive pulmonary disease (serious illnesses involving the lungs) impose a considerable burden with regard to morbidity, mortality, and health care cost. In the year 2000, COPD exacerbations were responsible for 726,000 hospitalizations, and 119,000 deaths in the US. Based on data from the Agency for Healthcare Research and Quality, patients admitted to US hospitals for COPD in 2002 had a mean length of stay of 5.1 days and accounted for $15,400 in charges. Current management of COPD exacerbations includes bronchodilators, corticosteroids, and antibiotics. Because leukotrienes (substances in the blood involved in inflammation) may play an important role in COPD exacerbations, we propose to study whether anti-leukotriene therapy provides additional benefit to usual care in the management of COPD exacerbations requiring inpatient care. The rationale for anti-leukotriene therapy in acute exacerbations of COPD is based on studies of mediators of inflammation in COPD, on clinical trials of anti-leukotriene therapy in COPD, and on a clinical trial of anti-leukotriene therapy in exacerbations of asthma. The motivation for identification of a novel therapeutic approach to COPD exacerbations is that a reduction in hospital length of stay should result in significant cost savings in the management of this common condition. We propose a parallel group, double blind, placebo-controlled randomized trial of the effects of a 14 day course of zileuton (600mg given orally 4 times a day) in addition to usual care vs placebo (an inactive pill) in addition to usual care in the management of COPD exacerbations requiring inpatient care. Patients will be enrolled in the study within 12 hours of admission to Harbor-UCLA Medical Center. The primary outcome will be duration of hospitalization. Approximately 520 subjects will be enrolled (approximately 60 at this center) over 18 months.